"This is the first time we've shown the relationship between obesity and Alzheimer's disease as measured by blood biomarker tests," said Cyrus Raji, M.D., Ph.D., senior author of the study and a principal investigator in the Neuroimaging Labs Research Center at Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine in St. Long-Term Brain Imaging and Blood Data To explore this connection, the team drew on five years of data from 407 volunteers enrolled in the Alzheimer's Disease Neuroimaging Initiative, which provided both amyloid positron emission tomography (PET) scans and blood samples.
PET scans are used to show the brain's amyloid burden, meaning the buildup of beta-amyloid protein in the brain as amyloid plaques, a key feature of Alzheimer's disease. Researchers analyzed plasma samples for several BBMs related to Alzheimer's disease, including pTau217 levels (a biomarker used in the diagnosis and monitoring of Alzheimer's disease), neurofilament light chain (NfL) -- a protein fragment released from damaged or dying neurons -- and plasma GFAP -- a protein expressed primarily in astrocytes (cells that support and protect neurons in the brain and spinal cord) using six leading commercial tests.
Linking Body Weight to Brain Biomarkers The research team used statistical methods to examine how these BBMs related to body mass index (BMI) and to evaluate a three-way interaction between baseline obesity, time and BBMs. They also compared and confirmed the BBM results against the amyloid PET scan findings. When they combined the blood and imaging data, they found that at the start of the study, higher BMI was linked to lower BBM levels and a lower overall amyloid burden across the brain.
"We believe the reduced BBMs in obese individuals was due to dilution from the higher blood volume," said study lead author Soheil Mohammadi, M.D., M.P.H., postdoctoral research associate at MIR. "In fact, by relying on the baseline measurements, you could be fooled into thinking that the people with obesity had a lower pathology of Alzheimer's disease.
We need the longitudinal data to fully understand the how obesity impacts the development of Alzheimer's pathology." A longitudinal study involves repeatedly collecting data from the same group over an extended period, tracking changes and trends over a period of time. Obesity Speeds Up Alzheimer's-Related Changes As the years passed, both Alzheimer's disease BBMs and brain PET scans showed a greater build-up of Alzheimer's-related pathology in participants with obesity compared with those without obesity.
People with obesity experienced a 29% to 95% faster increase in plasma pTau217 ratio levels. Having obesity at baseline was also associated with a 24% faster rise in plasma NfL and a 3.7% faster increase in amyloid accumulation. Raji noted that their results showed blood tests offered greater sensitivity than PET scans for detecting the influence of obesity on Alzheimer's-related brain changes.
"The fact that we can track the predictive influence of obesity on rising blood biomarkers more sensitively than PET is what astonished me in this study," he said. Clinical Implications and Modifiable Risk According to Dr. Mohammadi, the way obesity shapes the progression of amyloid burden and related shifts in Alzheimer's blood biomarkers has important implications for how clinicians assess and manage risk.
"According to the 2024 report of the Lancet Commission, 14 modifiable risk factors total approximately 45%, or close to half, of the risk for Alzheimer's disease," he said. "If we can reduce any of those risk factors, we can significantly reduce Alzheimer's cases or lengthen the amount of time until the onset of the disease." Future of Brain Health Monitoring and Treatment Dr.
Raji anticipates that repeated measurements of blood biomarkers, combined with brain imaging, will increasingly be used to track treatment strategies involving anti-amyloid drugs. "This is such profound science to follow right now because we have drugs that can treat obesity quite powerfully, which means we could track the effect of weight loss drugs on Alzheimer's biomarkers in future studies," he said.
"It's marvelous that we have these blood biomarkers to track the molecular pathology of Alzheimer's disease, and MRI scans to track additional evidence of brain degeneration and response to various treatments. This work is foundational for future studies and treatment trials." Other co-authors are Farzaneh Rahmani, M.D., M.P.H., Mahsa Dolatshahi, M.D., M.P.H., and Suzanne E.
Schindler, M.D., Ph.D.
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